All lesions of naturally occurring Murine Chronic Respiratory Disease (MCRD) have been reproduced in our laboratory by intranasal inoculation of pure cultures of Mycoplasma pulmonis into rats and mice reared and maintained under conditions which exclude all other pathogens. Furthermore, a highly reproducible model of respiratory mycoplasmal infection has now been established both in the mouse and the rat. Recent availability of these model systems provides an unusual opportunity for study of chronic pulmonary inflammation. The recognized morphologic similarities of chronic bronchitis and emphysema in man, and chronic respiratory disease of rats and mice, further strengthens the usefulness of these models. While data obtained using these models may not be directly applicable to man, they should provide insights into basic and essentially unexplored pathogenetic mechanisms of chronic lung disease. The present research program will utilize these model systems to define: (1) the initial injury and sequential development of lung lesions; (2) the immunological, inflammatory, and microbial mechanisms responsible for the production of these lesions; and (3) the type and function of reactive cells seen in chronic respiratory disease of rats and mice.